**4. Trial on effectiveness of Continuous Subcutaneous Insulin infusion (CSII) vs. multiple boluses of rapid insulin analog plus once daily basal insulin in T2D**

The effectiveness of CSII in T2D was sought for in many previous studies [48–52]. Our (Medtronic supported) prospective single-centre randomized study (2011–2014) [53–55] recruited 36 insulin-resistant, C-peptide-positive, glutamic acid decarboxylase antibodies (GAD Ab)-negative, and CSII-naive patients with T2D (eight screen failures). Insulin treatment was optimized with insulin analogs and metformin. Following the run-in period, patients were randomized into two arms: a CSII arm (n = 11) and an MDI continuation arm (n = 12). HbA1c ≥ 64 mmol/mol, (mean ± standard deviation), age of 57.2 ± 8.0 years, BMI of 36.2 ± 7.0 kg/m2 , BM of 106.9 ± 18.3 kg, diabetes duration of 13.3 ± 4.7 years, and HbA1c of 80 mmol/mol). In both arms, at the CSII start the daily insulin dose was reduced by 10% –50% in order not to exceed 80 U/day. After 6 months, persons receiving MDI crossed over to insulin pump and both arms were followed up during consequent 6 months. A total of 10 scheduled visits were carried out in each arm. The final Visit 10 occurred at 12 months. The mean frequency of self-monitoring varied between 3.4 and 5.4 measurements per day.

Patients assigned to the CSII arm (N = 11) achieved a significant HbA1c reduction of 10–12 mmol/mol while reducing their daily insulin dose by 33% of baseline; BMI reduction was 0.86% of baseline. No significant changes were revealed in patients on MDI **Figure 16**.

So, the use of insulin pump (supported with SMBG) in T2D is safe and effective for improving glucose control and reducing daily dose of insulin. Treatment adherence and satisfaction were excellent. All subjects decided to continue using their insulin pumps. On the other hand, an optimum metabolic balance and sustainable reduction in body mass, blood pressure or lipid profile in most of the patients could not be reached.

**15**

**Figure 16.**

*Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020*

**5. Case reports targeting incretin analogs/GLP-1 receptor agonists**

*continuous subcutaneous insulin infusion; MDI - multiple daily injections [55] (2017).*

to confirm their benefits in several persons.

sufficient reduction of body mass and HbA1c.

**5.1 Effects of liraglutide on body mass and HbA1c**

The first incretin analogs exenatid [56], lixisenatid, liraglutide were used in persons with T2D to improve metabolic control and to reduce body mass - mostly when HbA1c exceeded 60 mmol/mol, BMI was over 35 kg/m2 and oral antidiabetic drugs failed. Their beneficial metabolic and cardiovascular effects were described recently in RCTs LEAD 1 – LEAD 6 [57–62] and LEADER. [63] We had the option

*HbA1c (top) and total daily insulin dose (bottom) in the MDI/CSII arm (N = 11, closed symbols) and in the CSII/CSII arm (N = 11, open symbols). Symbols and bars - mean and 95% CI (confidence interval); CSII -* 

Our case report from the year 2010 [64] demonstrates the benefits of treatment with liraglutide in a 57-year old obese woman (adequately treated for hypothyreosis) with recent evolution of metabolic syndrome. Four-month metformin (M) and liraglutide (L) therapy reduced both body mass index (**Figure 17**), and glycated haemoglobin (**Figure 18**) Even though the previous diabetes control was acceptable, the treatment with high doses oť metformin and sitagliptin (S) failed to reach

*DOI: http://dx.doi.org/10.5772/intechopen.96237*

*Pathophysiologic Approach to Type 2 Diabetes Management: One Centre Experience 1980–2020 DOI: http://dx.doi.org/10.5772/intechopen.96237*

**Figure 16.**

*Type 2 Diabetes - From Pathophysiology to Cyber Systems*

hypo−/hyperglycemic episodes did not change.

described and discussed. [45, 46]

therapeutic regimen.

**basal insulin in T2D**

patients on MDI **Figure 16**.

of baseline HbA1c, insulin dose and BMI were found.

insulin in the course of FIASP therapy was shown.

tion), age of 57.2 ± 8.0 years, BMI of 36.2 ± 7.0 kg/m2

concentrations in 10-point profiles, daily insulin dose, BMI, and frequency of

insulin in intensive (complementary) treatment in individuals with T2D.

**3.3 Trial on effectiveness of Faster (ultrarapid) Insulin ASPart (FIASP)**

The benefits of faster insulin aspart (insulin aspart + nicotinamid) were

Aim of our prospective monocentric uncontrolled Real World Evidence study (2017–2019) [47] was to compare the efficacy of FIASP with the efficacy of previous therapy with insulin aspart in people with T1D and T2D on MDI or on insulin pump. No adverse events appeared in any group. In T2D groups (N < 24) an unsignificant tendency to reduction of PG, MPG, HbA1c, body mass and total daily dose of

So, only the evidence of noninferiority of FIASP versus insulin aspart was demonstrated. Introduction of improved algorithms together with intensive patients´ education appears necessary to improve the expected outcomes of FIASP

**4. Trial on effectiveness of Continuous Subcutaneous Insulin infusion (CSII) vs. multiple boluses of rapid insulin analog plus once daily** 

duration of 13.3 ± 4.7 years, and HbA1c of 80 mmol/mol). In both arms, at the CSII start the daily insulin dose was reduced by 10% –50% in order not to exceed 80 U/day. After 6 months, persons receiving MDI crossed over to insulin pump and both arms were followed up during consequent 6 months. A total of 10 scheduled visits were carried out in each arm. The final Visit 10 occurred at 12 months. The mean frequency

Patients assigned to the CSII arm (N = 11) achieved a significant HbA1c reduction of 10–12 mmol/mol while reducing their daily insulin dose by 33% of baseline; BMI reduction was 0.86% of baseline. No significant changes were revealed in

So, the use of insulin pump (supported with SMBG) in T2D is safe and effective for improving glucose control and reducing daily dose of insulin. Treatment adherence and satisfaction were excellent. All subjects decided to continue using their insulin pumps. On the other hand, an optimum metabolic balance and sustainable reduction in body mass, blood pressure or lipid profile in most of the patients could

of self-monitoring varied between 3.4 and 5.4 measurements per day.

The effectiveness of CSII in T2D was sought for in many previous studies [48–52]. Our (Medtronic supported) prospective single-centre randomized study (2011–2014) [53–55] recruited 36 insulin-resistant, C-peptide-positive, glutamic acid decarboxylase antibodies (GAD Ab)-negative, and CSII-naive patients with T2D (eight screen failures). Insulin treatment was optimized with insulin analogs and metformin. Following the run-in period, patients were randomized into two arms: a CSII arm (n = 11) and an MDI continuation arm (n = 12). HbA1c ≥ 64 mmol/mol, (mean ± standard devia-

, BM of 106.9 ± 18.3 kg, diabetes

No significant influence of insulin aspart on serum concentrations of triacylglycerols, total cholesterol, and LDL-cholesterol was found. Patients' satisfaction was good. No adverse events were recorded. In the control group, no significant changes

Hence, insulin analog aspart appears to be more effective than human regular

**14**

not be reached.

*HbA1c (top) and total daily insulin dose (bottom) in the MDI/CSII arm (N = 11, closed symbols) and in the CSII/CSII arm (N = 11, open symbols). Symbols and bars - mean and 95% CI (confidence interval); CSII continuous subcutaneous insulin infusion; MDI - multiple daily injections [55] (2017).*
